鼻腔节 extracellular matrix 促进心脏起器表型,并保护工程心脏组织中的自动性免受循环应变
Yao-Hui Sun1, Hillary K J Kao1, Phung N Thai2
1Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, Davis, CA 95616, USA; Institute for Regenerative Cures and Stem Cell Program, University of California, Davis, Sacramento, CA 95817, USA.
鼻腔节 Extracellular Matrix (ECM) 促进心脏肌细胞的节拍功能,并保护它们免受压力. 使用SAN ECM的工程组织保持了自动性和关键基因表达,与使用左心室ECM的组织不同.
科学领域:
- 心血管生物学 心血管生物学
- 生物材料科学 生物材料科学
- 再生医学是一种再生医学.
背景情况:
- 鼻腔节点 (SAN) 细胞外基质 (ECM) 对于支持本源节律心肌细胞 (PCM) 至关重要.
- 了解SAN ECM在PCM表型和功能中的特定作用对于心脏组织工程至关重要.
研究的目的:
- 研究SAN ECM对PCM表型和功能的促进和保护作用.
- 设计重建的SAN心脏组织 (rSANHTs) 并评估它们在机械应力下的性能.
主要方法:
- 通过重新细胞化猪 SAN ECM 与人类诱导的多能干细胞衍生的 PCM (hiPSC-PCM) 来进行工程化rSANHTs.
- 将rSANHT中的hiPSC-PCM与重建的左心室心脏组织 (rLVHTs) 的hiPSC-PCM进行了比较.
- 评估PCM自动性,心脏起器特异性基因表达和组织对循环应变的反应,通过移植到小鼠腹膜.
主要成果:
- rSANHTs中的hiPSC-PCMs自组织成类似SAN的集群,与rLVHTs相比表现出增强的节拍器基因表达和更快的自动性.
- 所有紧张的rSANHT保留了自动性,而66%的紧张的rLVHT失去了它.
- 紧张rSANHTs中的PCM保持了关键心脏起器基因 (HCN4,TBX3,TBX18) 的高表达,与紧张rLVHTs中的基因不同.
结论:
- 复合SAN ECM在维护PCM表型和功能方面发挥着重要的促进作用.
- SAN ECM提供了对机械应变的保护作用,保持了心脏自动性.
- 这些发现为推进节拍组织工程策略提供了有价值的见解.
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